Survey of Ophthalmology
Volume 49, Issue 2, Supplement 2 , Pages S73-S78 , March 2004

Fluoroquinolones: mechanism of action, classification, and development of resistance

  • Joseph M. Blondeau, MSc, PhD, RSM (CCM), SM (AAM), FCCP

      Affiliations

    • Corresponding Author InformationReprint address: Joseph M Blondeau, MSc, PhD, RSM (CCM), SM (AAM), FCCP, Royal University, 103 Hospital Drive, Saskatoon, SK, S7N 0W8 Canada.

References 

  1. Appelbaum PC, Hunter PA. The fluoroquinolone antibacterials: past, present and future perspectives. Int J Antimicrob Agents. 2000;16:5–15
  2. Ball P. Quinolone generations: natural history or natural selection?. J Antimicrob Chemother. 2000;46:17–24
  3. Ball P, Fernald A, Tillotson GS. Therapeutic advances of new fluoroquinolones. Exp Opin on Investigational Drugs. 1998;7:761–783
  4. Blondeau JM. Expanded activity of the new fluoroquinolones: a review. Clin Therapeu. 1999;21:3–40
  5. Blondeau JM. A review of clinical trials with fluoroquinolones with an emphasis on new agents. Exp Opin on Investigational Drugs. 2000;9:383–413
  6. Breines DM, Ouabdesselam S, Ng EY, et al.  Quinolone resistance locus nfxD of Escherichia coli is a mutant allele of parE gene encoding a subunit of topoisomerase IV. Antimicrob Agents Chemother. 1997;41:175–179
  7. Chaudry NA, Flynn HW, Murray TG, et al.  Emerging ciprofloxacin-resistant Pseudomonas aeruginosa. Am J Ophthalmol. 1999;128:509–510
  8. Fisher LM, Heaton VJ. Dual activity of fluoroquinolones against Streptococcus pneumoniae. J Antimicrob Chemother. 2003;51:463–464
  9. Fukuda H, Kishii R, Takei M, et al.  Contributions of the 8-methoxy group of gatifloxacin to resistance selectivity, target peference and antibacterial activity against Streptococcus pneumonaie. Antimicrob Agents Chemother. 2001;45:1649–1653
  10. Goldstein MH, Kowalski RP, Gordon YJ. Emerging fluoroquinolone resistance in bacterial keratitis. Ophthalmology. 1999;106:1313–1318
  11. Hirai K, Aoyana H, Irikura T, et al.  Differences insusceptibility to quinolones of outer membrane mutants of Salmonella typhimurium and Escherichia coli. Antimicrob Agents Chemother. 1986;29:535–538
  12. Hirai K, Suzue S, Irikura T, et al.  Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1987;31:582–586
  13. Hooper DC. Mechanisms of fluoroquinolone resistance. Drug Resist Updates. 1999;2:38–55
  14. Hooper DC, Wolfson JS. Fluoroquinolone antimicrobial agents. N Engl J Med. 1991;324:384–394
  15. Ito K, Hirai K, Inoue M, et al.  In vitro antibacterial activity of AM-715, a new nalidixic acid analog. Antimicrob Agents Chemother. 1980;17:103–108
  16. Jacobs MR, Bajaksouzian S, Zilles A, et al.  Susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae to 10 oral antimicrobial agents based on pharmacodynamic parameters: 1997 U.S. Surveillance Study. Antimicrob Agents Chemother. 1999;43:1901–1908
  17. Kampranis SC, Maxwell A. Conformational changes in DNA gyrase revealed by limited proteolysis. J Biol Chem. 1998;273:22606–22614
  18. Kato JI, Suzuki H, Ikeda H. Purification and characterization of DNA topoisomerase IV in Escherichia coli. J Biol Chem. 1993;267:25676–25684
  19. Khodursky AB, Zechdiedrich EL, Cozzarelli NR. Topoisomerase IV is a target of quinolones in Escherichia coli. Proc Natl Acad Sci USA. 1995;92:11801–11805
  20. King DE, Malone R, Lilley SH. New classification and update on the quinolone antibiotics. Am Fam Physician. 2000;61:2741–2748
  21. Korten V, Huang WM, Murray BE. Analysis by PCR and direct DNA sequencing of gyrA mutations associated with fluoroquinolone resistance in Enterococcus faecalis. Antimicrob Agents Chemother. 1994;38:2091–2094
  22. Leeming JP. Treatment of ocular infections with topical antibacterials. Clin Pharmacokinet. 1999;37:351–360
  23. Leibowitz HM. Clinical evaluation of ciprofloxacin 0.3% ophthalmic solution for treatment of bacterial keratitis. Am J Ophthalmol. 1992;112(Suppl):34S–47S
  24. Marlans KJ, Hiasa H. Mechanism of quinolone action—a drug-induced structural pertubation of the DNA precedes strand cleavage by topoisomerase IV. J Biol Chem. 1997;272:9401–9409
  25. Mather R, Karenchak LM, Romanowski EG, Kowalski RP. Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol. 2002;133:463–466
  26. Ng EY, Trucksis M, Hooper DC. Quinolone resistance mutations in topoisomerase IV: relationship of the flqA locus and genetic evidence that topoisomerase IV is the primary target and DNA gyrase the secondary target of fluoroquinolones in Staphylococcus aureus. Antimicrob Agents Chemother. 1996;40:1881–1888
  27. Norris S, Mandell GL. The Quinolones: History and Overview. London: Academic Press Ltd; 1998; pp 1–22
  28. O'Brien TP, Maquire MG, Fink NE, et al.  Efficacy of ofloxacin versus cefazolin and tobramycin in the therapy of bacterial keratitis. Report from the Bacterial Keratitis Research Group. Arch Ophthalmol. 1995;113:1257–1265
  29. Pan X, Fisher ML. Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: selective targeting of gyrase or topoisomerase IV by quinolones. Antimicrob Agents Chemother. 1997;41:471–474
  30. Piddock LJ, Wise R. The effect of altered porin expression in Escherichia coli upon susceptibility to 4-quinolones. J Antimicrob Chemother. 1986;18:547–549
  31. Schmidt FJ, Hofmann B, Hansen B, et al.  Relationship between ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin MICs and mutations in grlA, grlB, gyrA and gyrB in 116 unrelated clinical isolates of Staphylococcus aureus. J Antimicrob Chemother. 1998;41:481–484
  32. Smith A, Pennefather PM, Kaye SB, Hart CA. Fluoroquinolones: place in ocular therapy. Drugs. 2001;61:747–761
  33. Smith HJ, Nichol KA, Hoban DJ, Zhanel GG. Dual activity of fluoroquinolones against Streptococcus pneumoniae: the facts behind the claims. J Antimicrob Chemother. 2002;49:893–895
  34. Wang JC. DNA topoisomerases. Ann Rev Biochem. 1996;65:635–692
  35. Wang JC, Lynch AS. Transcription and DNA supercoiling. Curr OpinGenet Dev. 1993;3:764–768
  36. Willmott CJ, Maxwell A. A single point mutation in the DNA gyrase A protein greatly reduces binding of fluoroquinolones to the gyrase-DNA complex. Antimicrob Agents Chemother. 1993;37:126–127
  37. Yoshida H, Bogaki M, Nakamura M, et al.  Quinolone reistance-determining region in the DNA gyrase gyrB gene of Escherichia coli. Antimicrob Agents Chemother. 1991;35:1647–1650
  38. Yoshida H, Bogaki M, Nakamura M, Nakamura S. Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli. Antimicrob Agents Chemother. 1990;34:1271–1272
  39. Zechiedrich EL, Cozzarelli NR. Roles of topoisomerase IV and DNA gyrase in DNA unlinking during replication in Escherichia coli. Genes Dev. 1995;9:2859–2869

☆ The author reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. The author has received a research grant and is on the speaker bureau of numerous pharmaceutical companies, including Allergan, Inc.

PII: S0039-6257(04)00006-2

doi: 10.1016/j.survophthal.2004.01.005

Survey of Ophthalmology
Volume 49, Issue 2, Supplement 2 , Pages S73-S78 , March 2004

Article Tools

* Image Usage & Resolution